|Entry||Database: PDB / ID: 6mnx|
|Title||Structural basis of impaired hydrolysis in KRAS Q61H mutant|
|Keywords||HYDROLASE / GTPASE KRAS HYDROLYSIS|
|Function / homology|
Function and homology information
endocrine signaling / forebrain astrocyte development / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / negative regulation of epithelial cell differentiation / type I pneumocyte differentiation / positive regulation of Rac protein signal transduction / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of glial cell proliferation ...endocrine signaling / forebrain astrocyte development / regulation of synaptic transmission, GABAergic / epithelial tube branching involved in lung morphogenesis / negative regulation of epithelial cell differentiation / type I pneumocyte differentiation / positive regulation of Rac protein signal transduction / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of glial cell proliferation / Signaling by RAS GTPase mutants / Signaling by RAS GAP mutants / Activation of RAS in B cells / RUNX3 regulates p14-ARF / RAS signaling downstream of NF1 loss-of-function variants / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / glial cell proliferation / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Estrogen-stimulated signaling through PRKCZ / homeostasis of number of cells within a tissue / Signaling by PDGFRA extracellular domain mutants / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / SHC-mediated cascade:FGFR3 / Signaling by FGFR4 in disease / MET activates RAS signaling / SHC-mediated cascade:FGFR2 / Erythropoietin activates RAS / SHC-mediated cascade:FGFR4 / Signaling by FLT3 ITD and TKD mutants / SHC-mediated cascade:FGFR1 / Signaling by CSF3 (G-CSF) / FRS-mediated FGFR3 signaling / Tie2 Signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / FRS-mediated FGFR1 signaling / G protein activity / Signaling by FGFR2 in disease / striated muscle cell differentiation / GRB2 events in EGFR signaling / Ras activation upon Ca2+ influx through NMDA receptor / SHC1 events in EGFR signaling / p38MAPK events / Signaling by FLT3 fusion proteins / FLT3 Signaling / EGFR Transactivation by Gastrin / small monomeric GTPase / GRB2 events in ERBB2 signaling / Signaling by FGFR1 in disease / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / NCAM signaling for neurite out-growth / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / visual learning / regulation of long-term neuronal synaptic plasticity / RAF activation / FCERI mediated MAPK activation / Signaling by ERBB2 TMD/JMD mutants / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / MAP2K and MAPK activation / Ca2+ pathway / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / extrinsic component of cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / GDP binding / Negative regulation of MAPK pathway / regulation of protein stability / RAS processing / Signaling by RAF1 mutants / actin cytoskeleton organization / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by moderate kinase activity BRAF mutants / Signaling by BRAF and RAF1 fusions / MAPK cascade / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / DAP12 signaling / Ras protein signal transduction / neuron apoptotic process / RAF/MAP kinase cascade / mitochondrial outer membrane / negative regulation of neuron apoptotic process / GTPase activity / positive regulation of protein phosphorylation / Golgi membrane / focal adhesion
Similarity search - Function
Small GTPase, Ras-type / small GTPase Ras family profile. / Rho (Ras homology) subfamily of Ras-like small GTPases / Small GTPase / Ras family / Small GTP-binding protein domain / P-loop containing nucleotide triphosphate hydrolases / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
GUANOSINE-5'-TRIPHOSPHATE / GTPase KRas
Similarity search - Component
|Biological species||Homo sapiens (human)|
|Method||X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.2 Å|
|Authors||Bera, A.K. / Westover, K.D.|
|Citation||Journal: Cancer Res. / Year: 2020|
Title: KRASQ61HPreferentially Signals through MAPK in a RAF Dimer-Dependent Manner in Non-Small Cell Lung Cancer.
Authors: Zhou, Z.W. / Ambrogio, C. / Bera, A.K. / Li, Q. / Li, X.X. / Li, L. / Son, J. / Gondi, S. / Li, J. / Campbell, E. / Jin, H. / Okoro, J.J. / Xu, C.X. / Janne, P.A. / Westover, K.D.
|Structure viewer||Molecule: |
Downloads & links
A: GTPase KRas
B: GTPase KRas
C: GTPase KRas
D: GTPase KRas
E: GTPase KRas
F: GTPase KRas
A: GTPase KRas
B: GTPase KRas
C: GTPase KRas
D: GTPase KRas
E: GTPase KRas
F: GTPase KRas
Mass: 19281.777 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KRAS, KRAS2, RASK2 / Production host: Escherichia coli (E. coli) / References: UniProt: P01116
Mass: 523.180 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C10H16N5O14P3 / Comment: GTP, energy-carrying molecule*YM
|#4: Water|| ChemComp-HOH / |
|Experiment||Method: X-RAY DIFFRACTION / Number of used crystals: 1|
|Crystal||Density Matthews: 2.27 Å3/Da / Density % sol: 45.93 %|
|Crystal grow||Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5 |
Details: 0.1M MMT, 24% PEG 6000 and 1% 1,2-butanediol, pH 6.5
|Diffraction||Mean temperature: 293 K / Serial crystal experiment: N|
|Diffraction source||Source: SYNCHROTRON / Site: APS / Beamline: 19-ID / Wavelength: 0.9795 Å|
|Detector||Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Mar 16, 2017|
|Radiation||Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray|
|Radiation wavelength||Wavelength: 0.9795 Å / Relative weight: 1|
|Reflection||Resolution: 2.19→50 Å / Num. obs: 54159 / % possible obs: 99.1 % / Redundancy: 10.4 % / Biso Wilson estimate: 30.58 Å2 / CC1/2: 0.92 / Rpim(I) all: 0.032 / Net I/σ(I): 24.66|
|Reflection shell||Resolution: 2.2→2.24 Å / Redundancy: 4.5 % / Mean I/σ(I) obs: 2 / Num. unique obs: 2368 / CC1/2: 0.73 / Rpim(I) all: 0.351 / % possible all: 89.3|
|Refinement||Method to determine structure: MOLECULAR REPLACEMENT|
Starting model: 4obe
Resolution: 2.2→47.91 Å / SU ML: 0.278 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 27.0459
|Solvent computation||Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å|
|Displacement parameters||Biso mean: 43.79 Å2|
|Refinement step||Cycle: LAST / Resolution: 2.2→47.91 Å|
|Refine LS restraints|
|LS refinement shell|
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